Neoadjuvant Nivolumab plus Chemotherapy Achieves Promising Responses in Resectable NSCLC (CheckMate-816)

Patients with resectable early-stage NSCLC treated with nivolumab plus chemotherapy before surgery achieve higher rates of pathologic complete responses versus patients receiving chemotherapy alone.

CheckMate-816 is an ongoing phase 3 randomized open-label multicenter clinical trial that is evaluating nivolumab (Opdivo) plus chemotherapy compared with chemotherapy alone as neoadjuvant treatment in patients with resectable NSCLC.¹ The study is enrolling patients aged ≥18 years with resectable stage IB, II, or IIIA NSCLC, Eastern Cooperative Oncology Group performance status 0 or 1, pulmonary function capable of tolerating lung resection, and available lung tumor tissue.¹ Patients are ineligible for CheckMate-816 if they have an autoimmune disease or had received previous treatment with immune checkpoint inhibitors.¹

In the primary analysis, 358 patients were randomized to receive either nivolumab (360 mg intravenous) plus histology-based platinum doublet chemotherapy every 3 weeks for up to 3 doses, or platinum doublet chemotherapy every 3 weeks for up to 3 doses, followed by surgery.² The primary end points of the trial are pathologic complete response and event-free survival. Key secondary end points include OS, major pathologic response, and time to death or distant metastases.¹

In October 2020, it was announced that the CheckMate-816 trial met one of the primary end points, pathologic complete response.² Significantly more patients treated with nivolumab plus chemotherapy before surgery demonstrated no evidence of disease in their resected tissue compared with patients treated with chemotherapy alone.² The safety profile of nivolumab plus chemotherapy was described as consistent with previously reported studies in NSCLC.²

Positive findings in this phase 3 trial represent the first evidence that an immune checkpoint inhibitor–based combination offers superior efficacy compared with chemotherapy in the neoadjuvant setting for patients with resectable NSCLC.² CheckMate-816 is ongoing in order to assess the second primary end point, event-free survival, as well as key secondary end points. Investigators expect to present results of the CheckMate-816 trial at an upcoming medical conference.²

References
1. Felip E, Brahmer J, Broderick S, et al. CheckMate 816: a phase 3 trial of neoadjuvant nivolumab plus ipilimumab or chemotherapy vs chemotherapy in early-stage NSCLC. J Thorac Oncol. 2018;13:S831-S832.
2. Bristol-Myers Squibb. Opdivo (nivolumab) plus chemotherapy shows statistically significant improvement in pathologic complete response as neoadjuvant treatment of resectable non-small cell lung cancer in phase 3 CheckMate-816 trial. October 7, 2020. https://news.bms.com/news/corporate-financial/2020/Opdivo-nivolumab-Plus-Chemotherapy-Shows-Statistically-Significant-Improvement-in-Pathologic-Complete-Response-as-Neoadjuvant-Treatment-of-Resectable-Non-Small-Cell-Lung-Cancer-in-Phase-3-CheckMate--816-Trial/default.aspx. Accessed November 8, 2020.